1. Field of the Invention
The present invention relates to a medical adhesive which comprises a polyion complex film formed from a polycationic substance and a polyanionic substance. The medical adhesive of the present invention, which is in the form of film, absorbs blood or exudate from living tissues at the affected part and sticks to the tissue surface as it gels. It is particularly suitable for use as a tissue adhesive for surgical operations.
2. Discussion of the Background
Conventional tissue adhesives for surgical operations are illustrated below.
A typical one is so-called fibrin glue composed of fibrinogen, blood coagulation factor XIII, and thrombin. It is commercially available from several producers. Containing fibrinogen derived from human plasma, it has a disadvantage of being possibly infected with pathogenic organisms. In addition, it necessitates a step of mixing several materials immediately before use. This is troublesome.
Another one is cyanoacrylate-based tissue adhesive, which is also commercially available. It cures fast and provides high bond strength, but it has a disadvantage of evolving harmful formaldehyde upon decomposition in the living body.
A new product in the Japanese market is a tissue adhesive composed of gelatin, resorcinol, and formaldehyde. It also poses a problem with toxicity due to formaldehyde. In addition, it necessitates a step of mixing several reagents immediately before use. This is troublesome.
A tissue adhesive based on diisocyanate-urethane prepolymer is disclosed in Japanese Patent Laid-open No. 290465/1985, U.S. Pat. No. 4740534, and U.S. Pat. No. 4806614. It has not yet been put to practical use because it evolves, upon decomposition, diisocyanate which may be carcinogenic.
Conventional tissue adhesives shown above have many problems with biological safety (e.g., infection, sensitization, and toxicity) and handling properties.
In the meantime, it is well known that a polyion complex is formed rapidly when a polycationic substance and a polyanionic substance are mixed together in the presence of water. The polyion complex finds use in many application areas including drugs and medical instruments. An example of it is a polymeric composite material obtained by reaction between an anionic partial substitution product of dextran and a cationic partial substitution product of polysaccharide, which is used as a hemostatic in the form of powder, granules, or tablets, as disclosed in Japanese Patent Laid-open No. 110693/1978. Another example is aqueous solutions of polyanionic material and polycationic material (containing a calcium salt solution) which form a wound protecting layer when sprayed together on a wound, as disclosed in Japanese Patent Laid-open No. 73665/1986. The above-mentioned conventional polyion complex is applied in the form of powder or formed in situ on the wound from two solutions mixed together. On gelation, it merely gives rise to a gel which is not strong enough to be used as a tissue adhesive.
Another application of the polyion complex is in the active ingredient of an agent to promote regeneration of periodontal tissues by injection into periodontal pockets, as disclosed in Japanese Patent Laid-open No. 287538/1991. However, nothing is disclosed about use as a tissue adhesive.
A multilayered body for wound treatment is disclosed in Japanese Patent Laid-open No. 224293/1996. It is composed of chitosan, alginic acid, and chitin which arc arranged one over another on a substrate. It is produced by coating the substrate with chitin (or chitin dispersion) and then with a previously prepared chitosan-alginic acid complex, and finally drying the thus formed laminate. Since chitosan and alginic acid are not dissolved in water when they are made into a complex, they do not form a polyion complex in the multilayer body for wound treatment.